Membrane filtration is a separation technique widely used both for bench scale as well as process scale purification of biological materials. There are different types of membranes used in filtration, which are classified as microfiltration or ultrafiltration membranes depending on the pore size. Microfiltration membranes generally have pore size ranging between 0.1 μm and 10 μm; whereas, ultrafiltration membranes have a much smaller pore size, ranging between 0.001 and 0.1 μm. Because of the difference in the pore size, these membranes are used for different purposes. For example, microfiltration membranes are generally used for clarification, sterilization, and removal of microparticulates or for cell harvesting and ultrafiltration membranes are generally used for fractionation or for concentrating molecules (such as, for example, proteins, peptides, nucleic acids, carbohydrates, and other biological materials). Ultrafiltration membranes are typically classified by molecular weight cutoff, rather than pore size.
There are two main types of filtration modes which are generally employed with microfiltration and ultrafiltration membranes. One of the filtration modes is called Normal Flow Filtration (NFF) mode, also known as “dead-end” filtration, which generally applies the feed stream perpendicular to the membrane face and attempts to pass 100% of the fluid through the membrane. Another filtration mode is called Tangential Flow Filtration (TFF), where the feed stream is parallel to the membrane face, where one portion passes through the membrane (i.e., permeate) while the remainder is retained and may be recirculated back to the feed reservoir (i.e., retentate).
TFF mode of filtration is preferred for the purification of certain types of biological materials, for example those having a size of 500 kDa or larger than 500 kDa, where TFF is employed for concentration and impurity clearance. Most TFF applications employ ultrafiltration membranes which are useful for concentration and buffer exchange steps etc. One example of an ultrafiltration membrane which is used in TFF mode for manufacturing of certain biological materials (e.g., proteins, vaccines and virus-like particles) is a solution immersion cast ultrafiltration membrane made from polyethersulfone (PES).
Most ultrafiltration membranes widely used in TFF mode are required to be shipped in wet state and also with preservatives to prevent contamination by micoorganisms. However, not only is shipping in wet state difficult as it requires controlling the environmental conditions to prevent drying out and freezing of the membrane but the preservatives added to the membrane material often have to be removed prior to use in the purification of biological materials in order to avoid the preservatives from ending up in the sample containing the final product, e.g., a therapeutic protein or a vaccine.